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Individualized therapy in patients with primary membranous nephropathy


- candidate number25237
- NTR NumberNTR6078
- ISRCTNISRCTN no longer applicable
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR31-aug-2016
- Secondary IDs2014-1418 commissie CMO Arnhem-Nijmegen.
- Public TitleIndividualized therapy in patients with primary membranous nephropathy
- Scientific TitleAntibody guided therapy in patients with primary membranous nephropathy (MN)
- ACRONYMAntibody guided therapy in MN
- hypothesisIn 70 % of patients anti-PLA2R antibodies (aPLA2R) can be identified. Although spontaneous remissions do occur, up to 50 % of patients may need immunosuppressive therapy. The KDIGO guideline recommend initial therapy with a 6-month course of alternating monthly cycles of an alkylating agent and steroids. In the literature different treatment protocols with variable duration of drug therapy are used, however in all studies treatment was not personalized. In previous studies it was shown that disappearance of aPLA2R preceded clinical remission by 2-3 months. We observed that in the majority of patients treated with cyclophosphamide (CP) and mycofenolic acid (MMF) aPLA2R disappeared after 2 months. We use an antibody guided therapy protocol in patients treated with CP, MMF and tacrolimus. We expect that this will shorten the duration of therapy in many patients.
- Healt Condition(s) or Problem(s) studiedPrimary membranous nephropathy
- Inclusion criteria- patients with primary membranous nephropathy
- 18 years or older
- anti-PLA2R antibodies positive
- high risk of disease progression. High risk is defined as patients with a persisting nephritic syndrome (>6 months) despite conservative treatment, an urinary βeta-2-microglobulin (β2m) excretion of >1000 ng/min or deteriorating kidney function, or severe symptoms related to the nephrotic syndrome.
- Exclusion criteria- anti-PLA2R antibodies negative
- participation in another clinical trial
- mec approval receivedyes
- multicenter trialno
- randomisedno
- groupParallel
- Type2 or more arms, non-randomized
- Studytypeintervention
- planned startdate 30-aug-2013
- planned closingdate1-jun-2018
- Target number of participants100
- InterventionsSince august 2013 we use aPLA2R response to determine treatment duration in the individual patient. In the case of treatment with CP and MMF (both in combination with steroids), aPLA2R are measured after resp. 8, 16 and 24 weeks with a commercial IFT. If antibodies are negative the CP/MMF is stopped and the steroids are tapered. If the aPLA2R antibodies are still positive after 24 weeks of treatment and no complete remission is achieved further treatment with another agent is recommended. A maximum treatment duration of 6 months after the achievement of a partial remission is prescribed.
In case of tacrolimus (also in combination with prednisone); aPLA2R are measured after 24 weeks. If antibodies are negative the tacrolimus and the steroids are tapered. If the aPLA2R are still positive after 24 weeks of treatment further treatment is recommended and aPLA2R are measured again after 48 weeks. If, after 48 weeks of treatment continuation of treatment is recommended and aPLA2R are measured again after 48 weeks. If, after 48 weeks of treatment aPLA2R are still positive and no complete remission is achieved, further treatment with Rituximab (1000 mg) is recommended and the tacrolimus and the steroids are tapered.
For the cyclophamide group a comparison with a historical control group (treated with cyclophosphamide and steroids for 6-12 months) will be made.
- Primary outcome- Cumulative incidence of remissions (complete- and partial remission), for a duration of at least 6 months. Complete remission (CR) is defined as a protein-creatinine ratio ≤0.2 g/10 mmol creatinine with stable kidney function, and partial remission (PR) is defined as protein-creatinine ratio <3.0 g/10 mmol creatinine with a reduction of >50 % from baseline and stable kidney function. Achieving remission includes both partial and complete remission)
- Secondary outcome- duration of immunosuppressive treatment
- duration till disappearance of anti-PLA2R antibodies
- relapse rate (Relapse is defined as nephrotic proteinuria and an increase of > 50 % compared with the lowest value during remission)
- number of patients in need of additional therapy
- renal function deterioration ((1) a rise in serum creatinine >50%, or 2) a rise in serum creatinine >25% and an absolute level ≥135 Ámol/l)
- End-stage renal disease: eGFR <15 ml/min/1.73m2
- Adverse events
- Amount of remissions five years after the start of the initial treatment, with less than the standard immunosuppressive therapy.
- Timepoints24 months
- Trial web sitenot applicable
- statusopen: patient inclusion
- CONTACT FOR PUBLIC QUERIES Anne-Els van de Logt
- CONTACT for SCIENTIFIC QUERIES Anne-Els van de Logt
- Sponsor/Initiator Radboud University Medical Center Nijmegen
- Funding
(Source(s) of Monetary or Material Support)
Radboud University Medical Centre Nijmegen
- Publications
- Brief summaryIn 70 % of patients anti-PLA2R antibodies (aPLA2R) can be identified. Although spontaneous remissions do occur, up to 50 % of patients may need immunosuppressive therapy. The KDIGO guideline recommend initial therapy with a 6-month course of alternating monthly cycles of an alkylating agent and steroids. In the literature different treatment protocols with variable duration of drug therapy are used, however in all studies treatment was not personalized. In previous studies it was shown that disappearance of aPLA2R preceded clinical remission by 2-3 months. We observed that in the majority of patients treated with cyclophosphamide (CP) and mycofenolic acid (MMF) aPLA2R disappeared after 2 months. Since august 2013 we use aPLA2R response to determine treatment duration in the individual patient. We use an antibody guided therapy protocol in patients treated with CP, MMF and tacrolimus. We expect that we will shorten the duration of therapy in many patients.
- Main changes (audit trail)
- RECORD31-aug-2016 - 25-nov-2016


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